Department of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, 3 Blackfan Circle, Center for Life Science # 717, Boston, MA, 02215, USA.
Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1, Fukumuro, Miyagino-ku, Sendai, 983-8536, Japan.
Brain Struct Funct. 2019 Jan;224(1):99-110. doi: 10.1007/s00429-018-1766-2. Epub 2018 Oct 3.
Neurons containing melanin-concentrating hormone (MCH) in the posterior lateral hypothalamus play an integral role in rapid eye movement sleep (REMs) regulation. As MCH neurons also contain a variety of other neuropeptides [e.g., cocaine- and amphetamine-regulated transcript (CART) and nesfatin-1] and neurotransmitters (e.g., glutamate), the specific neurotransmitter responsible for REMs regulation is not known. We hypothesized that glutamate, the primary fast-acting neurotransmitter in MCH neurons, is necessary for REMs regulation. To test this hypothesis, we deleted vesicular glutamate transporter (Vglut2; necessary for synaptic release of glutamate) specifically from MCH neurons by crossing MCH-Cre mice (expressing Cre recombinase in MCH neurons) with Vglut2 mice (expressing LoxP-modified alleles of Vglut2), and studied the amounts, architecture and diurnal variation of sleep-wake states during baseline conditions. We then activated the MCH neurons lacking glutamate neurotransmission using chemogenetic methods and tested whether these MCH neurons still promoted REMs. Our results indicate that glutamate in MCH neurons contributes to normal diurnal variability of REMs by regulating the levels of REMs during the dark period, but MCH neurons can promote REMs even in the absence of glutamate.
位于下丘脑外侧后部的含黑色素浓缩激素（MCH）神经元在快速眼动睡眠（REMs）调节中发挥着重要作用。由于 MCH 神经元还含有多种其他神经肽[例如可卡因和安非他命调节转录物（CART）和 nesfatin-1]和神经递质（例如谷氨酸），因此负责 REMs 调节的特定神经递质尚不清楚。我们假设谷氨酸是 MCH 神经元中主要的快速作用神经递质，对于 REMs 的调节是必要的。为了验证这一假设，我们通过将 MCH-Cre 小鼠（在 MCH 神经元中表达 Cre 重组酶）与 Vglut2 小鼠（表达 LoxP 修饰的 Vglut2 等位基因）杂交，特异性地从 MCH 神经元中删除了囊泡谷氨酸转运体（Vglut2；谷氨酸突触释放所必需），并研究了基线条件下睡眠-觉醒状态的数量、结构和昼夜变化。然后，我们使用化学遗传学方法激活缺乏谷氨酸神经传递的 MCH 神经元，并测试这些 MCH 神经元是否仍然促进 REMs。我们的结果表明，MCH 神经元中的谷氨酸通过调节暗期 REMs 的水平，有助于 REMs 的正常昼夜变化，但即使没有谷氨酸，MCH 神经元也可以促进 REMs。
